[780] Evidence for Clonal Fibroblast Proliferation and Autoimmune Process in Idiopathic Retroperitoneal Fibrosis.

Jessica A Clevenger, Mingsheng Wang, Gregory T MacLennan, Rodolfo Montironi, Antonio Lopez-Beltran, Liang Cheng. Indiana University, Indianapolis; Case Western Reserve University, Cleveland, OH; Polytechnic University of the Marche Region, Ancona, Italy; Cordoba University, Spain

Background: Idiopathic retroperitoneal fibrosis is a rare disease in which retroperitoneal structures are encased by fibrosis and chronic inflammation. Its etiology is unclear. This study seeks to better characterize the disease process through clonality studies and IgG4 analysis. First, we sought to determine if idiopathic retroperitoneal fibrosis is a clonal fibroblast proliferation by performing X-chromosome inactivation analyses. Second, IgG4-related sclerosing diseases have been well established at other body sites, so we sought to determine if idiopathic retroperitoneal fibrosis is an IgG4-driven process.
Design: Forty-five cases of idiopathic retroperitoneal fibrosis diagnosed between 1991 and 2010 were retrieved from the surgical pathology archives of the participating institutions. Cases with known causes of secondary fibrosis were excluded. Clonality studies were restricted to female patients and were performed on 18 specimens from 16 patients. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. X-chromosome inactivation analyses were performed on fibroblasts within the fibrous. IgG4 and ALK immunohistochemistry was performed on 30 specimens from 28 patients. IgG immunohistochemistry was performed only on the cases with positive IgG4 staining. The patients ranged in age from 19 to 71 years (mean 53 years) and included both males and females (M:F=1.46:1).
Results: For the clonality analysis, 17 specimens were informative and 1 specimen was non-informative. 8 cases (47%) showed non-random X-chromosome inactivation. Two separate specimens were received in one of the 8 cases showing non-random X-chromosome inactivation, and concordant X-chromosome inactivation patterns were observed. Of the 30 specimens for which IgG4 analysis was performed, 16 cases (53%) were positive for IgG4-positive plasma cells. All 30 specimens were negative for ALK. Of the cases positive for IgG4, IgG staining was also performed, and the IgG4:IgG ratio ranged from 0.30 to 1.00 (mean 0.83).
Conclusions: Our clonality analysis indicates that a significant proportion of cases of idiopathic retroperitoneal fibrosis are associated with a clonal expansion of fibroblasts. Our finding of IgG4-positive plasma cells in 53% of the cases provides evidence that a subset of idiopathic retroperitoneal fibrosis cases could be classified in the IgG4-related sclerosing disease spectrum.
Category: Genitourinary (including renal tumors)

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 124, Monday Morning


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